Multifunctional neural networks underlie a variety of rhythmic behaviors and while anatomically hard-wired, they are functionally flexible. This proposal examines cellular mechanisms of flexibility in the mammalian respiratory system. One important modulator of respiration is oxygen level. In vivo, the respiratory system response to repetitive episodes of low oxygen, is a long lasting facilitation (LTF) of respiratory activity that is serotonin dependent. In this proposal: (1) I will determine if the respiratory system in the isolated rhythmic brain stem slice also expresses LTF following episodes of low oxygen. I will use whole cell patch clamp recordings to examine long term changes in activity of respiratory network and motor neurons as well as respiratory frequency. (2) I will use pharmacological techniques to determine if the LTF is serotonin dependent. (3) I will determine cellular mechanisms underlying LTF by using current and voltage clamp recordings to determine if there are changes in bursting properties, ion channels and/or synaptic transmission in respiratory network neurons. This work will increase our knowledge of respiratory network modulation, and will contribute to our understanding of disorders such as sleep apnea, since it is thought an enhancement of serotonergic drive to the respiratory system following periods of low oxygen may be a response to sleep apnea episodes.